Our general objectives are to continue our studies on the biochemical and structural mechanisms of the pathologic effects produced by ethanol with an interdisciplinary team with special expertise in hepatology, gastroenterology, pathology, biochemistry, nutrition, immunology and endocrinology. Our ultimate goal is the application of this information to the prevention and treatment of diseases associated with alcoholism. We plan to utilize to that effect our newly developed baboon model in which we have produced all the liver lesions seen in the alcoholic, namely the fatty liver, the hepatitis and the cirrhosis. We will determine when decompensation of liver functions occurs and liver injury ensues and at what point the lesions become irreversible. Parameters to be used for early aspects of liver injury will include the capacity of the liver to secrete lipids and proteins. The possible role of immunological reactions and mitochondrial injury in the development of alcoholic liver diseases will be assessed. The importance of nutritional factors in the development, aggravation and/or prevention of liver injury will be determined. We will also seek recognition of a precirrhotic lesion. Once cirrhosis is established, the nature of the abnormality in collagen and ground substance metabolism will be studied. Both pharmacologic and dietary approaches to the prevention of cirrhosis will be attempted. Occurrence and reversibility of portal hypertension will be assessed. Androgen and estrogen abnormalities associated with cirrhosis will be evaluated through measurements of hormone levels and clearance rates in the blood and enzyme activities in the liver. The respective role of alcohol and malnutrition in the development of gastrointestinal and muscle lesions will be evaluated. Whenever possible, our baboon model will also be made available as a resource to other interested investigators for the study of the effects of alcohol abuse on other tissues, for behavioral assessments and the correlation of behavioral parameters with biochemical changes. BIBLIOGRAPHIC REFERENCES: Lieber, C.S., Rubin, E., DeCarli, L.M. and Feinman, L. Respective roles of ethanol and protein deficiency in the pathogenesis of alcoholic hepatitis and cirrhosis. In Diseases of the Liver and Biliary Tract. (C.M. Leevy, ed.) S. Karger AG, Basel, Switzerland, pp. 97-100, 1976. Cederbaum, A.I., Lieber, C (Text Truncated - Exceeds Capacity)